The present invention relates to a pharmaceutical composition which adheres only to a gastric mucosa and duodenal mucosa and is controlled in the release of its medicament.
When effective use of a medicament is considered, a preparation controlled in the release of the medicament thereof, particularly, a sustained release preparation has great advantages such as decrease in the frequency of administration, maintenance of the blood level for a predetermined time and the like, because it can continuously release the medicament over long hours. Sustained release preparations have therefore been investigated from various aspects.
Since the medicament of a sustained release preparations is mainly absorbed at the intestine, many of the preparations are designed to gradually release the medicament while they pass through the whole digestive tract. On the contrary, preparations designed to exhibit their efficacy not after adsorbed by the intestine but topically at the stomach or duodenum are not so many.
As a preparation intended to cause the medicament to act in the stomach, reported have been a preparation having intragastric retention heightened by imparting it with a floating property (Daviss S S et al. Pharm. Res. 208-213(1986)), a preparation whose contact ratio to the surface of a mucosa has been improved by increasing the specific gravity of it (Devereux J E et al. Pharmacol, 42, 500-501(1990)) and the like. These preparations however are not sufficient in retention.
In addition, a preparation which adheres onto the mucosa of a digestive tract by gelation of a polymer, which has been incorporated in the preparation, with water has been proposed (Japanese Patent Application Laid-Open No. Hei 5-132416). This preparation however lacks in adhesion selectivity to an intended digestive tract so that it is impossible to adhere this preparation only to the gastric and duodenal mucosae.
An object of the present invention is therefore to provide a preparation which adheres only to the gastric and duodenal mucosa, is controlled in the release of its medicament and has excellent pharmacological effects selectively for the stomach and duodenum.
With the foregoing in view, the present inventors have carried out an extensive investigation. As a result, it has been found that by controlling the release of a medicament by an ingredient selected from water insoluble polymers, polyglycerin fatty acid esters, lipids and waxes, and imparting the medicament with selective adhering capacity only to the gastric and duodenal mucosae by using a polymer which adheres to the surface of the mucosa of a digestive tract under acid conditions but does not adhere under neutral or alkali conditions, the medicament acts on the gastric and duodenal mucosa over long hours but quickly excreted from the intestine, which makes it possible to provide a preparation exhibiting high pharmacological action at a low concentration of the medicament, leading to the completion of the present invention.
The present invention therefore provides a gastric and/or duodenal adhesive pharmaceutical composition obtained by coating a composition, which contains a medicament exhibiting action in the stomach and/or duodenum and an ingredient selected from water insoluble polymers, polyglycerin fatty acid esters, lipids and waxes, with a polymer which has adhering capacity to the surface of the mucosa of a digestive tract under acid conditions but separates from the mucosa of the digestive tract under neutral or alkaline conditions.